Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/21127
Title: Genetically Determined Risk of Depression and Functional Outcome After Ischemic Stroke.
Authors: Gill, Dipender;James, Nicole E;Monori, Grace;Lorentzen, Erik;Fernandez-Cadenas, Israel;Lemmens, Robin;Thijs, Vincent N;Rost, Natalia S;Scott, Rodney;Hankey, Graeme J;Lindgren, Arne;Jern, Christina;Maguire, Jane M
Affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, United Kingdom
Department of Neurology, Neurovascular Research Laboratory and Neurovascular Unit, Universitat Autònoma de Barcelona, Vall d'Hebrón Hospital, Spain
Stroke Pharmacogenomics and Genetics, Institut d'investigació Biomedica de Sant Pau, Hospital de Sant Pau, Barcelona, Spain
Bioinformatics Core Facility, University of Gothenburg, Sweden
University of Technology Sydney, Faculty of Health, Sydney, Australia
Hunter Medical Research Institute, University of Newcastle, Australia
Priority Research Centre for Stroke and Traumatic Brain Injury, University of Newcastle, Australia
Department of Neurology and Rehabilitation Medicine, Neurology, Skåne University Hospital, Lund, Sweden
Department of Clinical Sciences Lund, Neurology, Lund University, Sweden
Department of Clinical Pathology and Genetics, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Sweden
Faculty of Medicine, Imperial College London, United Kingdom
Department of Medicine, Neurovascular Research Laboratory and Neurovascular Unit, Universitat Autònoma de Barcelona, Vall d'Hebrón Hospital, Spain
Department of Neurosciences, Experimental Neurology, University of Leuven, Belgium
Center for Brain and Disease Research, Laboratory of Neurobiology, Leuven, Belgium
Department of Neurology, University Hospitals Leuven, Belgium
Stroke Division, The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Heidelberg, Australia
Department of Neurology, Austin Health, Heidelberg, Victoria, Australia
Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston
School of Medicine and Public Health, University of Newcastle, Australia
Hunter Medical Research Institute, University of Newcastle, Australia
Medical School, The University of Western Australia, Perth
From the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, United Kingdom
Bioinformatics Core Facility, University of Gothenburg, Sweden
Issue Date: 26-Jun-2019
EDate: 2019-06-26
Citation: Stroke 2019; online first: 26 June
Abstract: Background and Purpose- Psychosocial factors can have implications for ischemic stroke risk and recovery. This study investigated the effect of genetically determined risk of depression on these outcomes using the Mendelian randomization (MR) framework. Methods- Genetic instruments for risk of depression were identified in a discovery genome-wide association study of 246 363 cases and 561 190 controls and further replicated in a separate population of 474 574 cases and 1 032 579 controls. Corresponding genetic association estimates for risk of ischemic stroke were taken from 60 341 cases and 454 450 controls, with those for functional outcome 3 months after ischemic stroke taken from an analysis of 6021 patients. Following statistical power calculation, inverse-variance weighted MR was performed to pool estimates across different instruments. The Cochran Q heterogeneity test, weighted median MR, and MR pleiotropy residual sum and outlier were used to explore possible bias relating to inclusion of pleiotropic variants. Results- There was no MR evidence for an effect of genetically determined risk of depression on ischemic stroke risk. Although suffering low statistical power, the main inverse-variance weighted MR analysis was suggestive of a detrimental effect of genetically determined risk of depression on functional outcome after ischemic stroke (odds ratio of poor outcome [modified Rankin Scale, ≥3] per 1-SD increase in genetically determined risk of depression, 1.81; 95% CI, 0.98-3.35; P=0.06). There was no evidence of heterogeneity between MR estimates produced by different instruments (Q P=0.26). Comparable MR estimates were obtained with weighted median MR (odds ratio, 2.57; 95% CI, 1.05-6.25; P=0.04) and MR pleiotropy residual sum and outlier (odds ratio, 1.81; 95% CI, 0.95-3.46; P=0.08). Conclusions- We found no MR evidence of genetically determined risk of depression affecting ischemic stroke risk but did find consistent MR evidence suggestive of a possible effect on functional outcome after ischemic stroke. Given the widespread prevalence of depression-related morbidity, these findings could have implications for prognostication and personalized rehabilitation after stroke.
URI: http://ahro.austin.org.au/austinjspui/handle/1/21127
DOI: 10.1161/STROKEAHA.119.026089
ORCID: 0000-0002-6614-8417
PubMed URL: 31238828
Type: Journal Article
Subjects: depression
morbidity
stroke
Appears in Collections:Journal articles

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